Preliminary studies have shown that the beta-adrenergic blocking drugs, propranolol, nadolol and metoprolol, are inhibitors of calmodulin activated calcium ATPase. Propranolol is a beta blocker which appears to be useful in the treatment of psychiatric disorders and thus apparently has central nervous system (CNS) effects in addition to its actions on the heart, while metoprolol is an example of a relatively cardiospecific beta-blocker. We have found that increasing cardiospecificity in the three beta blockers named above is accompanied by decreasing potency in the inhibition of the calmodulin - calcium ATPase test system. We propose to examine a larger series of beta blockers to determine whether the correlation holds. If it does, we anticipate that inhibition of calmodulin activated calcium ATPase will be a useful tool in the development and application of beta blockers which will have either relatively pure CNS actions or relatively pure cardioselectivity. The test system that we use allows the determination of the inhibition constants by a kinetic assay, in which a critical step is the computation (by a computer-assisted iterative program) of concentrations of unbound calmodulin prevailing during the assay.